Humoral Correlates of Protection Against Influenza A/H3N2 Virus Infection.

Publication date: Dec 16, 2024

Influenza virus remains a threat to human health, but gaps remain in our knowledge of the humoral correlates of protection against influenza virus A/H3N2, limiting our ability to generate effective, broadly protective vaccines. The role of antibodies against the hemagglutinin (HA) stalk, a highly conserved but immunologically subdominant region, has not been established for influenza virus A/H3N2. Household transmission studies were conducted in Managua, Nicaragua, across 3 influenza seasons. Household contacts were tested for influenza virus infection using reverse-transcription polymerase chain reaction. We compared preexisting antibody levels against full-length HA, HA stalk, and neuraminidase (NA) measured by enzyme-linked immunosorbent assay, along with hemagglutination inhibition assay titers, between infected and uninfected participants. A total of 899 individuals participated in household activation, with 329 infections occurring. A 4-fold increase in initial HA stalk titers was independently associated with an 18% decrease in the risk of infection (adjusted odds ratio [aOR], 0. 82 [95% confidence interval {CI}, .68-. 98]; P = .04). In adults, anti-HA stalk antibodies were independently associated with protection (aOR, 0. 72 [95% CI, .54-. 95]; P = .02). However, in 0- to 14-year-olds, anti-NA antibodies (aOR, 0. 67 [95% CI, .53-. 85]; P < .01) were associated with protection against infection, but anti-HA stalk antibodies were not. The HA stalk is an independent correlate of protection against A/H3N2 infection, though this association is age dependent. Our results support the continued exploration of the HA stalk as a target for broadly protective influenza vaccines but suggest that the relative benefits may depend on age and influenza virus exposure history.

Concepts Keywords
Adults Adolescent
Influenza Adult
Nicaragua Aged
Polymerase Antibodies, Viral
Vaccines Antibodies, Viral
Child
Child, Preschool
correlates of protection
Enzyme-Linked Immunosorbent Assay
Family Characteristics
Female
global health
Hemagglutination Inhibition Tests
Humans
Immunity, Humoral
Infant
influenza
Influenza Vaccines
Influenza Vaccines
Influenza, Human
Male
Middle Aged
Neuraminidase
Neuraminidase
Nicaragua
vaccination
Young Adult

Semantics

Type Source Name
pathway KEGG Influenza A
disease MESH Virus Infection
disease MESH Influenza
disease IDO role
disease IDO assay
disease MESH infections
disease IDO infection
disease IDO history
drug DRUGBANK Influenza A virus

Original Article

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